Background: Recent evidence has shown that the antimalarials are usefuldrugs in the treatment of various rheumatic diseases. The present study was designed to test the therapeuticeffect of pyrimethamine (PYR) in collagen-induced arthritis (CIA). Material/Methods: CIA was inducedin Lewis rats. The intraperitoneal administration of PYR and methotrexate (MTX) were started on day 25post-immunization and continued until final assessment on day 35. During this period, clinical examinationwas performed intermittently. Anti-C II Ab and nitric oxide (NO) synthesis were measured. The paws andknees were then removed for histopathology and radiography assay. The biocompatibility of PYR and MTXwere assessed using a fibrosarcoma cell line. Results: Data showed that i.p. injection of pyrimethamineto arthritic rats induced a significant reduction in paw edema. This beneficial effect was associatedwith a significant decrease in anti-CII antibody response compared with untreated rats. Histopathologicalassessment showed reduced inflammatory cell infiltrate in the joints of treated rats, and tissue edemaand bone erosion in the paws were markedly reduced following PYR therapy. Moreover, our radiography resultsparalleled our histological findings. Cytotoxicity analysis of PYR showed greater tolerability comparedwith MTX. Treatment with PYR significantly diminished nitric oxide formation in treated rats comparedwith untreated controls. Conclusions: Our findings shed light on the therapeutic efficacy of pyrimethaminein experimental rheumatoid arthritis compared with a choice drug (methotrexate), which may recommendedit as a second-line drug in the treatment of rheumatoid arthritis.

Keywords: Arthritis, Experimental - radiography, Antibodies - immunology, Arthritis, Experimental - radiography, Arthritis, Rheumatoid - radiography, Cell Survival - drug effects, Matrix Metalloproteinase 2 - metabolism, Nitric Oxide - blood, Pyrimethamine - therapeutic use, Rats, Inbred Lew